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LIU Chuan Yong 刘传勇 Institute of Physiology Medical School of SDU Tel 88381175 (lab) 88382098 (office) Email: [email protected] Website: www.physiology.sdu.edu.cn Section 4 Regulation of the Circulation Introduction The aim: to regulate the blood flow of organs to fit their metabolic requirement in different condition. The regulation of blood flow are of three major types: Neural Humoral Local I. Neural Regulation of the Circulation 1. Innervation of the Circulatory System Cardiac innervation Innervation of blood vessels Sympathetic vasoconstrictor fiber Sympathetic vasodilator fiber Parasympathetic nerve fiber to peripheral vessels Cardiac innervation Sympathetic nerve – noradrenergic fiber Parasympathetic nerve- cholinergic fiber Noradrenergic sympathetic nerve increase the cardiac rate (positive chronotropic effect) Increase the force of cardiac contraction (positive inotropic effect). Cholinergic vagal cardiac fibers decrease the heart rate. Cardiac innervation (contin.) At rest moderate amount of tonic discharge in the cardiac sympathetic nerves a good deal of tonic vagal discharge (vagal tone) When the vagi are cut in experiment animals, the heart rate rises Innervation of blood vessels Sympathetic vasoconstrictor fiber Distribution: Almost all segments of the circulation. The innervation is powerful in the kidneys, gut, spleen and skin, is less potent in both skeletal and cardiac muscle and in the brain. Innervation of blood vessels Sympathetic vasoconstrictor fiber (contin.) Almost all vessels, such as arteries, arterioles, venules and veins are innervated, except the capillaries, precapillary sphincters and most of the metarterioles. Tone: Usually the sympathetic vasoconstrictor fibers keep tonic. Innervation of blood vessels 2) Sympathetic vasodilator fiber The sympathetic nerves to skeletal muscles carry sympathetic vasodilator fibers as well as constrictor fibers. release acetylcholine at their endings and cause vasodilation. Importance: increase the blood flow in skeletal muscle during exercise and stress. Innervation of blood vessels 3) Parasympathetic nerve fiber to peripheral vessels Parasympathetic nerve fibers innervate vessels of the blood vessels in Meninges (脑膜, 髓膜) the salivary glands the liver the viscera in pelvis the external genitals Importance: Regulate the blood flow of these organs in some special situations. 2 Cardiovascular Center The control center of cardiovascular activities is the nucleus groups at different levels spinal cord brain stem hypothalamus limbic system cerebral cortex cerebellum Cardiovascular Center if the brain is sectioned at the level of the lower pons the blood pressure falls If the section at the level of the obex the fall in blood pressure is more profound Cardiovascular centers of the brainstem Medulla oblongata is essential to Cardiovascula r centers. Cardiovascular centers of the brainstem vasoconstrictor-area vasodilator area cardioinhibitory area relay station of afferent nerve 1.Rostral ventrolateral medulla, rVLM (Vasoconstrictor area): 2. Caudal ventrolateral medulla, cVLM (Vasodilator area) 3. NTS (nucleu of solitary tract relay station of afferent nerve) 4. Cardioinhibitory area 1). vasoconstrictor-area (rVLM) (neurotransmitter: NE neurons) (l) the cardiac sympathetic center (2) the sympathetic vasoconstrictor center 2).vasodilator area (cVLM) (NE neurons) to inhibit action of rVLM area → vasodilation 3).cardioinhibitory area (dorsal vagal nucleus and nucleus ambigulus) the cardial vagus center 4).relay station of afferent nerve NTS (nucleu of solitary tract) to accept and integrate afferent impulses and then affect other centers 3. Reflex Regulation of the Circulation Baroreceptor reflexes Reflex involving arterial chemoreceptors CNS ischemic response (1) Baroreceptor reflexes 1) Physiological anatomy of the baroreceptors. Carotid sinus At the bifurcation of the common carotid arteries the root of internal carotid artery shows a little bulge has stretch receptors in the adventitia are sensitive to arterial pressure fluctuations Carotid sinus. (contin.) Afferent nerves travel in the carotid sinus nerve a branch of the glossopharyngeal nerve. (IXth cranial nerve) Aortic arch. baroreceptors in the adventitia of the arch of aorta Function similar to the carotid sinus receptors. afferent nerve fibers travel in the aortic nerve, a branch of the vagus nerve. (Xth cranial nerve) 2) buffer nerves Buffer nerves The carotid sinus nerves and vagal fibers from the aortic arch At normal blood pressure levels, the fibers discharge at a low rate. When the pressure rises, the discharge rate increases when the pressure falls, the rate declines Sinus Nerve response to Blood Pressure At 0 – 60 mmHg, no sensitive (aortic baroreceptors, 030mmHg). Between 60 to 80 mmHg: respond progressively more and more strongly. At 100 mmHg: The response is the greatest Above 180 mmHg: no further increase in response . 3) Relationship between the isolated carotid sinus pressure and the blood pressure Raising the carotid sinus pressure leads to a fall in arterial blood pressure. Lowering the carotid sinus pressure leads to a rise in arterial blood pressure CSP, carotid sinus pressure; FABP, femoral artery blood pressure Set point: The point where the carotic sinus (isolated) pressure and blood pressure are the same. 4) Concept and mechanism of baroreceptor reflex Any drop in systemic arterial pressure decreases the discharge in the buffer nerves, there is a compensatory rise in blood pressure and cardiac output. On the contrary the opposite Arterial Baroreceptor Pressure Vasoconstrictor Center Cardio-acceleratory Area Carotid Sinus Sinus Nerve Aortic Arch Vagus Nerve Peripheral Vascular Dilation Heart Rate Contractility Cardio-inhibitory Area + Peripheral Resistance ( R) Cardiac Output (Q) Arterial pressure decrease back towards normal (5) Importance of the baroreceptor reflex Tonic regulation of blood pressure keep the arterial pressure relatively constant Pressure buffer system – reduce the blood pressure fluctuation during the daily events, such as changing of the posture, respiration, excitement, and so forth. (6) Baroreceptor Resetting Baroreceptor will adapt to the long term change of blood pressure. if the blood pressure is elevated for a long period of time, several days or years, the set point will transfer to the elevated mean blood pressure. baroreceptor reflex is not a long term control system. unimportant for long-term regulation of arterial pressure (2) Reflex involving arterial chemoreceptors Chemoreceptors: situated in the carotid body and aortic body Reflex involving arterial chemoreceptors (contin.) • have a very rich blood supply, • ideal for sampling chemical changes in the blood. • sensitive to the decreased Po2, increased PCO2 and increased hydrogen ion concentration in the plasma. • Afferent: • carotid body afferent fiber - carotid sinus nerve --glossopharyngeal nerve. • Aortic body afferent fiber - aortic nerve – vagus nerve Reflex involving arterial chemoreceptors (contin.) Response: Stimulation of chemoreceptors leads to a reflex increase in vasomotor tone, causes generalized vasoconstriction and hence a rise in blood pressure. Importance: is important in regulation of blood pressure when it fall below the range in which baroreceptors act (70 mmHg). (3) CNS ischemic response Chemoreceptor reflex: useful in regulation of blood pressure when it falls to a level between 40 and 70 mmHg. But if the blood pressure below 40 mmHg, the last ray of hope for survival is the central nervous system (CNS) ischemia response. the “last ditch stand” pressure control mechanism. CNS ischemic response (contin.) evoked by ischemia (poor blood flow) of the central nervous system. Reduction in blood flow to the VMC leads to reduced Po2 elevated Pco2 stimulate the VMC directly, leading to vasoconstriction and consequently rise in blood pressure. II Chemical and hormonal control of cardiovascular function Introduction Various hormones, chemicals Start at a low pace, Have long-lasting influences Classification Vasoconstrictors Vasodilators Vasoconstrictors and Vasodilators Vasoconstrictors Epinephrine and Norepinephrine Angiotensin II Vasopressin Vasodilators EDRF (NO) Epinephrine and Norepinephrine The adrenal medulla secrete both epinephrine (80%) and norepinephrine (20%) carried by blood flow to everywhere in the body. In the blood, only a little norepinephrine comes form the endings of the adrenergic fibers. Adrenergic receptors Epinephrine Norepinephrine α1 receptor on vessels Vasoconstriction β1 receptor on heart Positive effect β2 receptor on vessels (skeletal muscle and liver) Vasodilation Effect On heart in vitro (contractility and automaticity). both increase the force and rate of contraction of the isolated heart. mediated by β1 receptors. Effect On peripheral resistance Norepinephrine produces vasoconstriction in most if not all organs via α1 receptors epinephrine dilates the blood vessels in skeletal muscle and the liver via β2 receptors overbalances the vasoconstriction produced by epinephrine elsewhere the total peripheral resistance drops Nor: On heart in vivo Ps and Pd increase – barorecepor reflex – bradycardia – override direct cardioacceleratory effect the heart rate and cardiac out falls. Epi: On heart in vivo causes a widening of the pulse pressure baroreceptor stimulation is insufficient to obscure the direct effect of the hormone on the heart, cardiac rate and output increase. Angiotensin II very potent vasoconstrictor formed in the plasma through a chain reaction. triggered by a substance, renin, released form kidneys. Renin is released from kidneys in response to renal ischemia, which may be due to a fall in blood pressure. Effect of Angiotensin II powerful constrictor release aldosterone from the adrenal cortex acts on the brain to create the sensation of thirst. inhibit the baroreceotor reflex and increase the release of norepinephrine from the sympathetic postganglionic fiber. Vasopressin antidiuretic hormone (ADH), formed in the hypothalamus (mainly) secreted through the posterior pituitary gland. more powerful than angiotensin as a vasoconstrictor. during hemorrhage – increased vasopressin - raise the arterial pressure as much as 40 to 60 mmHg. Vasopressin Vasoconstriction has not a physiological function does not increase blood pressure when small doses are injected in vivo In healthy person, the plasma concentration is too low to induce vasoconstrion Acts on the brain to cause a decrease in cardiac output. in the area of postrema Acts on the kidney – physiological (ADH) Endothelium – Derived Relaxing Factor Metabolism Effect of NO Relax the vascular smooth muscle directly Mediate vascular dilator effect of some hormones and transmitters (Ach, bradykinin, VIP, substance P) Inhibit the tonic excitation of some neurons in the vasomotor centre. Inhibit the norepinephrine release from the sympathetic postganglionic fiber. One or more of these effects are physiological. III Autoregulation of Local Blood Pressure Role of Vasodilator Substances. CO2, Lactic acid, Adnosine, Adnosine phosphate compounds, Histamine, K+ and H+ Myogenic Activity Heterometric autoregulation